Transplantation of cells and tissues from one human to another is limited by the host immune system, which identifies and rejects non-host cells and tissues with high efficiency. One strategy for avoiding or surmounting this barrier is to enclose the cells in a “cage” that provides a biological shield (an “immune shield”) that prevents the transplanted cells and tissues from being rejected by the host immune system. This strategy has application in endocrinology (e.g., islet cell transplantation), gene therapy (transplantation of cells to provide a missing protein or to replace a dysfunctional protein), immune therapy, or other biological therapy (transplantation of cells to provide specific active biological molecules, such as immunoglobulins, cytokines, immune regulators or biological response modifiers). Such a system could also provide a micro-environment, within a human or other host body, for tissue engineering, to allow for differentiation of cells or assembly of tissue structures with two-dimensional or three-dimensional architecture, or the formation of nascent organs, for subsequent use in the host or elsewhere.
Immune shielding may also serve as an important strategy for preventing immune rejection of implantable medical devices that range in size from ultra-small scale nanoparticles and nanoprobes to large scale macroscopic devices. The strategy of immune shielding allows use of a wider range of materials in the construction of implantable medical devices than would otherwise be possible because of the presence of the host immune system and therefore the potential for unwanted immune system responses.
Many materials have been proposed as immune shields, including specially treated biological and non-biological materials, silicon, ceramics, synthetic polymers and other non-organic materials. As a rule, these foreign materials tend to provoke an immune response in the host body, which has limited development in this field. Another phenomenon associated with transplantation of foreign materials into a host is localized scar formation (“fibrotic capsule formation”) and/or obstruction of pores in the foreign material. The presence of pores is required in most biological applications for efficient transfer of nutrients, gases and other biological factors into the interior of the cage, and efficient transfer of waste products, metabolites and secreted substances from inside the capsule to outside the cage.
What is needed is a biocompatible material that can be formed into a “cage” or similar structure for containing cells or tissue that prevents or limits access by the host immune system to the foreign cells or tissue. The capsule material should allow the cells and/or tissue to be maintained in a live and functioning state; and in some cases, should permit the cells and/or tissue to carry out normal (physiological) or specially engineered sensing functions and/or normal (physiological) or specially engineered secretory functions. The capsule material itself should not provoke (or should limit significantly) an immune response in the host system. The capsule material itself should not elicit (or should limit significantly) scar formation in the host that, together with an immune response, could lead to obstruction of the pores of the capsule material. The capsule material itself should resist protein deposition that, together with scar formation or an immune response, could lead to obstruction of the pores. Preferably, the material should be flexible and sufficiently resilient to withstand the forces that may be involved in surgical implantation or transplantation and other forces that may be present in the host environment. The material should be configurable into a variety of geometric shapes, to optimize transport of substances across the capsule and to promote the maintenance of cells and/or tissues.
U.S. Pat. No. 7,070,923 to Loftus describes the use of carbon nanotube Bucky paper for the transplantation or implantation of cells and/or tissues or medical devices, wherein containers for cells and/or tissues or medical devices are fabricated from multiple layers of flat pieces of carbon nanotube Bucky paper in a sandwich configuration. Three-dimensional structures made from flat pieces of carbon nanotube Bucky paper, such as tubes made by rolling up flat pieces of carbon nanotube Bucky paper, or rolls of Bucky paper with multiple spiral layers are also disclosed. However, the formation of 3-dimensional structures from flat pieces of Bucky paper requires potentially time-consuming and potentially labor intensive procedures to manipulate the flat pieces of Bucky paper. The formation of 3-dimensional structures from flat pieces of Bucky paper also requires seams between individual pieces of Bucky paper, either “edge to edge” seams or “overlapping seams,” and, in some cases, the use of additional materials such as suture or other ligature to close the seams. These seams may be undesirable, because they may constitute points or regions of structural weakness of the Bucky paper containers, which could result in rupture of the Bucky paper containers. In addition, the seams are undesirable because they may result in leakage or migration of the cells and/or tissue or medical devices from inside the Bucky paper containers to outside the Bucky paper containers. In addition, the seams may serve as points of entry of host immune system cells to the interior of the Bucky paper containers, which could result in an undesirable immune system response to the cells and/or tissues or medical devices contained therein.
U.S. Pat. No. 7,618,647 to Weber describes uses of Bucky paper on medical implants such as stents. The Bucky paper is applied by wrapping the stents with Bucky paper and securing the paper with clamps, sewing or glue. Nonplanar Bucky paper can allegedly be formed using a cylindrical or tubular filter, or by forming a filter into a pouch shape. Weber states that an implant can be placed inside the pouch and additional Bucky paper formed on top to enclose the implant. However, no method of forming Bucky paper on top of a pouch containing an implant is provided, and the methods otherwise disclosed for forming Bucky paper in situ would not be operable to close the top of a pouch in a leak-proof manner. Spraying techniques are also described where a suspension of nanotubes is sprayed onto an implant, the solvent dried and the nanotubes compressed onto the implant; however spraying, drying and compressing would damage the structure of the finished capsule, disrupting its integrity. Weber fails to disclose any means of creating a leak-proof capsule or enclosure for any device or bioactive structure or material.